April 6, 2005

Mr. Chairman and Members of the Committee:

I am pleased to present the Fiscal Year (FY) 2006 President's budget request
for the National Human Genome Research Institute (NHGRI). The FY 2006 budget
includes $490,959,000, an increase of $2,351,000 over the FY 2005 enacted level
of $488,608,000 comparable for transfers proposed in the President's request.

Cable News Network (CNN) recently named the completion of the Human Genome Project
(HGP) the number one health news story of the past 25 years. CNN reported, "Much
of the marvel of medicine has to do with discovery. Mapping the human genome,
the complete sequence of DNA, gave scientists a blueprint for building a person,
making it the No. 1 medical story, according to a distinguished panel CNN gathered
to rank the top 25 medical stories of the past quarter-century." As the
leader of the HGP, the National Human Genome Research Institute (NHGRI) is very
proud of this recognition, but as CNN also pointed out there is still a great
deal more to learn.

Ongoing NHGRI Initiatives

Analysis of the Completed Human Genome Sequence

In October 2004, the International Human Genome Sequencing Consortium, led
in the United States by the NHGRI and the Department of Energy, published a
description of the finished human genome sequence in the journal Nature. An
international team worked to convert the draft genome, published in 2001, into
a highly accurate form. The new analysis reduces the estimate of the number
of human protein-coding genes from 35,000 to only 20,000-25,000-a surprisingly
low number for our species, considering that only a decade ago most scientists
thought there would be over 100,000 genes. We now focus on the more difficult
task of understanding the function of each of these genes.

Use of Comparative Genomics to Understand the Human Genome

The availability of the genome sequences of the human, the mouse, the rat and
a wide variety of other organisms is driving the development of an exciting new
field of biological research, comparative genomics. The NHGRI is funding research
comparing the finished reference human genome sequence with that of other organisms,
to identify regions of similarity and difference, thus dramatically increasing
understanding of the structure and function of human genes to enable development
of new strategies to combat human disease.

ENCyclopedia Of DNA Elements (ENCODE) project

With the goal of identifying the precise location and function of all sequence-based
functional elements in the human genome, the NHGRI launched the ENCyclopedia Of
DNA Elements (ENCODE) project in the fall of 2003. The project is an international
consortium of computational and laboratory-based scientists open to all investigators
who agree to abide by the project's criteria and guidelines for participation.
A manuscript describing the ENCODE project appeared in the October 22, 2004 issue
of Science, detailing the rationale and strategy behind the quest to produce a
comprehensive catalog of all parts of the human genome crucial to biological function,
including all protein-coding genes, non-protein-coding genes, regulatory elements
involved in the control of gene transcription, and DNA sequences that mediate
chromosomal structure and dynamics. All data generated for the ENCODE project
are being deposited in free, public databases as soon as they are experimentally
verified.

Progress with the HapMap

All diseases have a hereditary component, but for most common diseases like
diabetes, heart disease, and mental illness, the gene variants responsible for
the increased risk have been difficult to identify. To solve this problem, an
approach to scan large regions of chromosomes to find the genetic variants (called
SNPs, or single nucleotide polymorphisms) that increase or decrease the risk
of disease is needed. NHGRI has taken a leadership role in the International
HapMap Consortium and the development of the HapMap (haplotype map), a catalog
of human genetic variations and how that is organized into haplotype "neighborhoods"
across the gene. Researchers are already starting to use the HapMap to find
genes and variants that contribute to many diseases; it will also be a powerful
resource for studying the genetic factors contributing to variation in individual
response to disease, drugs, and vaccines.

In February 2005, the International HapMap Consortium completed phase I of the
project, ahead of schedule. Boosted by an additional $3.3 million in public-private
support, the NHGRI announced plans to create an even more powerful map of human
genetic variation than originally envisioned. The consortium's new goal is an
improved version of the HapMap about five times denser than the original plan.
This "Phase II" HapMap will test another 4.6 million SNPs from publicly
available databases and add that information to the map. The HapMap will be
completed in the fall of 2005.

Gene Variants May Increase Susceptibility to Type 2 Diabetes

Understanding the genetic basis of the more common, polygenic diseases has traditionally been very difficult. But the tools of genomics, especially HapMap, are beginning to reveal many details about the risk of common diseases that had previously
been unapproachable. One disease for which excellent progress has been made
towards understanding its genetic cause is Type 2 diabetes. Affecting about
17 million people nationwide, it accounts for 90 to 95 percent of all diabetes
cases in the U.S. This past year, two international research teams, including
one at NHGRI, each found variants in a gene that appears to predispose people
to type 2 diabetes, the most common form of the disease. Homing in on a wide
stretch of chromosome 20, the teams identified four genetic variants (SNPs)
that are strongly associated with type 2 diabetes in Finnish and Ashkenazi Jewish
populations and that appear to raise the risk of type 2 diabetes by about 20
to 30 percent. Translating this discovery into a treatment that benefits people
with diabetes or those at risk is still years away, but this is a major step
in that direction.

New Initiatives

Roadmap - Chemical Genomics

The Molecular Libraries Roadmap initiative will offer public sector researchers
access to libraries of novel small organic molecules that can be used as chemical
probes to study the functions of genes, cells, and biochemical pathways. This
marriage of chemistry and biology will provide new ways to explore the functions
of major components of cells in health and disease. In June 2004, NHGRI announced
the establishment of the NIH Chemical Genomics Center, and up to eight pilot
extramural centers will be funded at academic institutions and other locations
across the country in the spring of 2005. These will function as an integrated
network, including a common publicly available database (PubChem, already activated
in September 2004) which will display the results of all screens of chemical
compounds.

Human Cancer Genome Project

The dramatic drop in costs of DNA sequencing, catalyzed by the Human Genome
Project, now makes it possible to use sequencing as a major tool for medical
research. Doctors and research scientists have long known that cancer is, essentially,
a genetic disease. Inherited mutations or acquired genetic alterations can set
a normal cell on a path of uncontrolled growth and malignancy. It is now conceivable
to identify the complete universe of genes involved in every type of cancer.
That is the intent of a bold new NCI/NHGRI proposal for a Human Cancer Genome
Project. Such a complete inventory of cancer genes will provide powerful new
ways to prevent, diagnose, and treat every major form of the disease.

The $1,000 Genome Project

The ability to determine the complete genome sequence of an individual could
revolutionize medical care. In October 2004, NHGRI awarded more than $38 million
in grants to spur the development of innovative technologies designed to reduce
the cost of DNA sequencing dramatically. NHGRI's near-term goal is to lower
the cost of sequencing a mammalian-sized genome to $100,000, which would enable
researchers to sequence the genomes of hundreds or even thousands of people
as part of studies to identify genes that contribute to cancer, diabetes, and
other common diseases. Ultimately, NHGRI's vision is to cut the cost of whole-genome
sequencing to $1,000 or less, which would enable the sequencing of individual
genomes as part of medical care. The ability to sequence each person's genome
cost-effectively could give rise to more individualized strategies for diagnosing,
treating, and preventing disease. Such information could enable doctors to tailor
therapies to each person's unique genetic profile.

The U.S. Surgeon General's Family History Initiative

The U.S. Surgeon General's Family History Initiative was launched on November
8, 2004, with the NHGRI as the lead collaborating federal agency. The purpose
of this national public health campaign is to: increase the awareness of the American
public and their health professionals about the importance of family history in
health; provide tools to gather, understand, evaluate, and use family history
to improve health; give health professionals tools to communicate with patients
about family history; and increase genomic and health literacy. A web based and
print tool entitled "My Family Health Portrait" was developed in both
English and Spanish to facilitate collection of family history data. To date,
the initiative has been highlighted in more than 1,000 media stories and over
170,000 copies of the tool have been distributed via the World Wide Web and in
paper form. This public health campaign is intended to be an annual event.

ELSI Centers for Excellence Program

On August 31, 2004, the NHGRI's Ethical Legal and Social Implications (ELSI)
research program announced the funding, with contributions from the Department
of Energy and the National Institute of Child Health and Human Development,
of four interdisciplinary centers as part of its Centers for Excellence in ELSI
Research (CEER) program, a new initiative to address some of the most pressing
ethical, legal, and social questions facing individuals, families, and communities
in the genome era. Each of the centers, based at Duke University, Case Western
Reserve University, Stanford University, and the University of Washington, will
assemble a team of experts in several disciplines, such as bioethics, law, behavioral
and social sciences, clinical research, theology, public policy, and genomic
research.

Other Areas of Interest

Genetic Education for Health Care Professionals

The NHGRI has developed numerous educational programs to prepare health care
professionals for the integration of genomics into primary health care. A new
effort by the NHGRI in this area in 2004 was its work with the American Academy
of Family Physicians (AAFP) to develop the AAFP's 2005 Annual Clinical Focus
program, which has Genomic Medicine as its theme.

Genetic Nondiscrimination

Possibly the greatest impediment to the advancement of genomic science and its
application to human health is the fear of genetic discrimination. The NHGRI
has worked for ten years to realize a federal solution to this problem. The
Secretary's Advisory Committee on Genetics Health and Society has also strongly
supported the need for federal legislation. On February 17, 2005 the Senate
passed the Genetic Information Nondiscrimination Act of 2005 (S. 306), which
would address these fears, and the Bill has now been referred to the House.
The Bush Administration has also issued a Statement of Administrative Policy
in support of the legislation. This issue remains a high priority for the Institute.

Thank you, Mr. Chairman. I would be pleased to answer any questions that the
Committee might have.

Professional History:

1977-1981, Intern, Resident, Chief Resident in Medicine, North Carolina Memorial
Hospital, Chapel Hill, North Carolina.
1981-1984, Fellow in Human Genetics and Pediatrics, Yale University School of
Medicine, New Haven, Connecticut.
1984-1993, Assistant, Associate and then Full Professor of Internal Medicine and
Human Genetics, University of Michigan, Ann Arbor, Michigan.
1987-1993 Assistant, Associate and then Full Investigator, Howard Hughes Medical
Institute.
1993 to present, Director, National Human Genome Research Institute, NIH, Bethesda,
Maryland.

Biographical Information:

Dr. Collins is a physician-geneticist that is noted for his landmark discoveries
of disease genes and his leadership of the Human Genome Project. With Dr. Collins
at the helm, the Human Genome Project consistently met projected milestones ahead
of schedule and under budget. This international project culminated in April 2003
with the completion of a finished sequence of the human genetic blueprint. From
its outset in 1990, the public sequencing effort swiftly deposited all of its
data into free, public databases for use by scientists around the world. Building
on the foundation laid by the Human Genome Project, Dr. Collins is now leading
the NHGRI effort to ensure that this new trove of sequence data is translated
into powerful tools and thoughtful strategies to advance biological knowledge
and improve human health.

Dr. Collins' own research initiatives have included the discovery of a number
of important genes, including those responsible for cystic fibrosis, neurofibromatosis,
Huntington's disease and most recently, the gene that causes Hutchinson-Gilford
progeria syndrome, a dramatic form of premature aging. In addition to his scientific
achievements, Dr. Collins is known for his continuing emphasis on the importance
of ethical and legal issues in genetics. He has been a strong advocate for protecting
the privacy of genetic information and has served as a national leader in efforts
to prohibit gene-based insurance and employment discrimination.

Professional Organizations:

American Society of Human Genetics; American Society for Clinical Investigation;
Association of American Physicians; Institute of Medicine; National Academy of
Sciences; American Academy of Arts and Sciences.

William R. Beldon

Department of Health and Human Services
Office of Budget

Mr. Beldon is currently serving as Deputy Assistant Secretary, Budget in the
Department of Health and Human Services. He has been a Division Director in
the Budget Office for sixteen years, most recently as Director of the Division
of Discretionary Programs. Mr. Beldon started in federal service as an auditor
in the Health, Education and Welfare Financial Management Intern program. Over
the course of more than 30 years in the Budget Office, Mr. Beldon has held Program
Analyst, Branch Chief and Division Director positions. Mr. Beldon received a
Bachelor=s Degree in History and Political Science from Marshall University
and attended the University of Pittsburgh where he studied Public Administration.
He resides in Fort Washington, Maryland.